一种溶瘤腺病毒抑制肿瘤细胞的作用机制及特异性研究
摘 要 研究重组人5型腺病毒(H101)抑制肿瘤细胞增殖的作用机制及特异性。采用体外细胞培养方法及TCID50检测病毒滴度法,发现H101对p53?的肿瘤细胞有显著的选择性复制作用,其活性可以对p53突变的肿瘤组织产生溶瘤作用从而达到治疗效果;采用体外药效学实验检测H101对10种肿瘤细胞株的抑增殖作用,通过计算IC50、IC90进一步得出小鼠肝癌细胞Hepa1-6、小鼠胰腺癌细胞Pan02、小鼠神经胶质瘤细胞GL261对H101较为敏感。研究结果表明H101对已获批的适应证之外的其他肿瘤细胞也有溶瘤作用,具有适应证扩展的潜力。本研究可为后续开展动物模型的体内药效实验和使用剂量的选择提供参考。关键词 溶瘤腺病毒 肿瘤治疗 体外药效学 增殖抑制
中图分类号:R979.19; R730.54 文献标志码:A 文章编号:1006-1533(2024)15-0065-04
引用本文 琚姝, 王爱霞. 一种溶瘤腺病毒抑制肿瘤细胞的作用机制及特异性研究[J]. 上海医药, 2024, 45(15): 65-68.
Study on the mechanism and specificity of an oncolytic adenovirus (recombinant human adenovirus type 5) inhibiting the proliferation of tumor cells
JU Shu, WANG Aixia
(Shanghai Sunway Biotech Co., Ltd., Shanghai 201206, China)
ABSTRACT The mechanism and specificity of human adenovirus type 5 (H101) in inhibiting tumor cells were studied. By in vitro cell culturation and TCID50 virus titer test, it was found that the oncolytic adenovirus had a significant selective replication effect on p53- tumor cells and its replication ability could produce oncolytic effect on p53 mutated tumor tissue and achieved therapeutic effect. In vitro pharmacodynamic experiment was used to detect the inhibitory effect of H101 on ten tumor cell lines. By calculating IC50 and IC90 ......
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